Method for preparing emulsions

ABSTRACT

The invention relates to a method and a system for the emulsification of a pre-mix of two or more immiscible liquids by flowing or circulating one or more times said pre-mix through one or more magnetic fields.

The present invention is in the field of the manufacture of emulsions.Particularly, the invention is in the field of preparing stableoil-in-water and water-in-oil emulsions. More specifically, theinvention relates to a method and a system for the preparation of stableemulsions by conducting an unstable pre-mixture of immiscible fluids,optionally containing solid particles, through one or more magneticfields.

BACKGROUND OF THE INVENTION

Emulsions may be broadly defined as metastable colloidal dispersions ofliquid droplets in another liquid phase. Typically, emulsions aredisperse systems comprising at least two liquids which are virtuallyinsoluble in one another. Besides the said at least two liquid phasecomponents and optionally solid particles and/or one or moreemulsifiers, the formation of an emulsion requires energy and occurs atconditions far from equilibrium. In general, the formation of anemulsion comprises the two following steps:

-   -   in an initial step, at least two components are pre-mixed, the        said at least two components being originally liquid phase        immiscible, the pre-mixing preferably being in the presence of a        suitable amount of one or more emulsifiers, in order to create        droplets of a dispersed liquid phase in another continuous        liquid phase;    -   thereafter, the droplets resulting from the initial step are        disrupted by shear forces or by local pressure differences, i.e.        by inertial forces, thus resulting in a more stable emulsion of        usually smaller droplets.

At present, different types of mechanical emulsification processes areused in the production of finely dispersed emulsions, each processrequiring specific equipment. Within these emulsification systems, fourmajor categories may be recognized:

-   -   droplet disruption in a high shear rotor-stator system,    -   droplet disruption by ultrasound,    -   droplet disruption in high-pressure systems, and    -   droplet formation at micropores (using microporous membranes or        microchannels).        Also non-mechanical processes may be applied, such as        precipitation of the dispersed phase previously dissolved in the        continuous phase, phase inversion method and phase inversion        temperature method.

Emulsions may either be produced directly as consumer products or asintermediates for use within a broad range of industrial applicationsincluding, in a far from exclusive list, food, paints, cosmetics,pharmaceuticals, explosives, rocket fuel, lubricants, foam-controllingagents, etc. Most industrial applications or consumer products requirethat emulsions have maximal storage stability. The storage stabilityrefers to the period of time during which the emulsion can be keptbefore it separates again into different phases. Mechanisms that can beidentified in the process of breaking down an emulsion include theso-called Ostwald ripening, creaming, aggregation, coalescence, andpartial coalescence. The process of breaking down an emulsion can beinfluenced or monitored, and therefore storage stability can becontrolled or increased, in the two following ways: using mechanicaldevices to control the size of the dispersed droplets and/or addingstabilising chemical additives or emulsifiers in order to keep theemulsion dispersed.

Emulsions have great importance in the plastics (i.e. polymers)industry, especially in the detergents and cleaning products industries,in the production of lubricants, cosmetic, veterinary or pharmaceuticalcompositions (e.g. creams and ointments) and, in particular, in foodproducts technology as well. Since many emulsions comprise at least onehydrophilic liquid and at least one lipophilic liquid, a furtherdistinction is usually made, depending on the nature of the internal,disperse phase, between oil-in-water emulsions and water-in-oilemulsions. The internal or the external phase of the emulsion may itselfin turn be a disperse system and may, for example, include particles ofsolids dispersed in the respective liquid phase, a system of this kindbeing also referred to as a multiphase emulsion. Owing to theinterfacial tension which exists between the droplets of the internalphase and the droplets of the continuous, external phase, emulsions arein general thermodynamically unstable and thus after some time a phaseseparation occurs which may be induced, for example, by dropletsedimentation or coagulation. In order to prevent such phase separationit is common, during emulsion manufacturing, to add emulsifyingauxiliaries, such as emulsifiers (which lower the interfacial tension)or stabilisers (which, for instance, prevent or at least greatly retardthe sedimentation of the droplets, by increasing the viscosity of thecontinuous, external phase).

When the at least two liquid phase components of an emulsion are mixedtogether, the initial result is a coarsely disperse crude emulsion. Bysupplying mechanical energy, the large drops of the crude emulsion arebroken up and the desired fine emulsion is formed. The smallest dropletsize achievable in the last step of the emulsification process dependsnot only on the respective input of power in the emulsifying equipmentbut can be also critically influenced by the nature and concentration ofthe emulsifying auxiliaries. For example, in order to produce ultra-thinemulsions, it is essential that the new interfaces which are formedmechanically be occupied very rapidly by the emulsifier in order toprevent coalescence of the droplets.

The average size of the droplets of the disperse phase can be determinedin accordance with the principle of quasi-elastic dynamic lightscattering, for instance by using a Coulter N4+ particle analysercommercially available from Coulter Scientific Instruments.

A wide variety of liquid dispersing machines are used for producingemulsions. Emulsions of medium to high viscosity are produced mainly bymeans of rotor-stator systems, such as colloid mills or gear-rimdispersing machines. Low-viscosity emulsions have to date been producedmainly using high-pressure homogenizers, in which case the crudeemulsion under a pressure of between about 100 bars and 1,000 bars isdischarged through the about 10 to 200 μm high radial gap of ahomogenizing nozzle. It is assumed that drop break-up in this case ismainly attributable to the effect of cavitation. One specific design ofa high-pressure homogenizer is the microfluidizer, which operates atrelatively low pressures of about 100 bars. However, high-pressurehomogenizers are not without disadvantages. Especially when emulsifyingpolymerizable systems or when producing multiphase emulsions includingsolid particles, the narrow radial gap of the homogenizing nozzle mayeasily become clogged. The subsequently required cleaning istime-consuming and complex. Moreover, the high pressures used in thistype of equipment entail sealing problems, especially when using liquidcomponents which attack the equipment sealants. A further disadvantageof high-pressure homogenizers is that drop size and throughput areclosely linked with each other. Such equipment is therefore unsuitablefor producing emulsions in whose disperse phase it is intended todisperse solid particles.

Liposomes may be defined as vesicles in which an aqueous volume isentirely enclosed by a bilayer membrane composed of lipid molecules.When dispersing these lipids in aqueous media, a population of liposomeswith sizes ranging from about 15 nm to about 1 μm may be formed. Thethree major types of lipids, i.e. phospholipids, cholesterol andglycolipids, are amphipathic molecules which, when surrounded on allsides by an aqueous environment, tend to arrange in such a way that thehydrophobic “tail” regions orient toward the center of the vesicle whilethe hydrophilic “head” regions are exposed to the aqueous phase.According to this mechanism liposomes thus usually form bilayers.

Several types of liposomes are known in the art. Referring to theirphysical structure, the more easily accessible type of liposomesconsists of multilamellar vesicles (hereinafter referred to as MLV,according to standard practice in the art), i.e. onion-like structurescharacterized by multiple membrane bilayers, each separated from thenext by an aqueous layer, usually having a size between about 100 nm and1 μm, which known e.g. from U.S. Pat. No. 4,522,803 and U.S. Pat. No.4,558,579. Their production can be reproducibly scaled-up to largevolumes and they are mechanically stable upon storage for long periodsof time.

By contrast, small unilamellar vesicles (hereinafter referred to as SUV,according to standard practice in the art) usually having a size betweenabout 15 nm and 200 nm, possess a single bilayer membrane and areusually difficult to prepare on a large scale because of the high energyinput required for their production and of the risks of oxidation andhydrolysis. In addition, SUV are thermodynamically unstable and aresusceptible to aggregation and fusion. Furthermore, as the curvature ofthe membrane increases in SUV, it develops a degree of asymmetry, i.e.the restriction in packing geometry dictates that significantly morethan 50% and up to 70% of the lipids making up the bilayer are locatedon the outside. Because of this asymmetry, the behaviour of SUV ismarkedly different from that of bilayer membranes comprising MLV or fromthat of large unilamellar vesicles (the latter, hereinafter referred toas LUV, usually having a size between about 100 nm and 1 μm).

Referring to their chemical structure, liposomes may be made fromneutral phospholipids, negatively-charged (acidic) phospholipids,sterols and other non-structural lipophilic compounds. For instance, apopulation of detergent-free liposomes having a substantially monomodaldistribution (i.e. unilamellar vesicles) about a mean diameter greaterthan 50 nm and exhibiting less than a two-fold variation in size may beproduced (e.g. according to EP-B-185,756) by first preparingmultilamellar liposomes and then repeatedly passing them under pressurethrough a filter having a pore size not more than 100 nm. For a detaileddescription of liposomes and methods of manufacturing them, reference ishereby made to Liposomes, a practical approach (1990), Oxford UniversityPress. Liposome manufacturing and quality control encounters many of thedifficulties set forth herein-above in respect of other dispersedsystems including multiphase emulsions.

Thus there is a need in the art for providing an economical and improvedalternative to the existing mechanical and non-mechanical processes formaking emulsions. In particular, there is a need in the art forproviding an emulsification process which avoids the requirement ofcomplex mechanical equipment and the associated maintenance costs, whileresulting in a desirable droplet size within a limited period of timeand simplifying its quality control procedure, and while achieving aprolonged storage stability of the resulting emulsion. There is also aneed in the art for modulating the characteristics, such as micellesize, of an emulsion either during or after its manufacturing. All theabove needs apply to liposome manufacturing as well, more specificallyincluding improving trapping efficiency and stability of multilamellarliposomes.

SUMMARY OF THE INVENTION

The deficiencies of the prior art as discussed above are overcome oralleviated by the method of the present invention, whereinstorage-stable emulsions may be produced by cost-efficient means byconducting or circulating a pre-mix, i.e. a usually unstable mixture, oftwo or more originally immiscible liquids through one or more magneticfields under conditions suitable for emulsifying the said pre-mix. In apreferred embodiment of the invention, the said pre-mix may furthercomprise one or more emulsifiers or emulsion stabilizers.

In a second aspect, there is provided a system for the preparation of anemulsion according to the method of the invention. Said emulsificationsystem comprises means for generating one or more magnetic fields, suchas a magnetic fluid conditioner, the said means being mounted in acircuit or loop comprising at least a liquid containing portion, i.e. areservoir or container, filled with two or more originally immiscibleliquids, the said system further comprising means whereby the two ormore liquids contained in the liquid containing portion can be conductedor circulated through the said one or more magnetic fields being forinstance generated by the magnetic fluid conditioner. Optionally, amixer may be mounted on the liquid containing portion of theemulsification system for stirring the two or more liquids containedtherein. In a preferred embodiment, the circuit or loop includes one ormore tubings, channels or ducts wherein the two or more liquids can flowfrom and back to the liquid containing portion, and the means forcirculating the two or more liquids through the magnetic field(s)includes one or more pumps mounted in the said circuit or loop. The saidpump(s) may be designed or operated such as to allow for controlling orregulating, e.g. keeping constant or else varying according to apredetermined scheme, the speed at which the two or more liquids areconducted or circulated through the magnetic field(s). In a morepreferred embodiment, the two or more liquids may be re-circulated oneor more times through the magnetic field(s) back into the liquidcontaining portion of the system, for instance until an emulsion withsuitable characteristics (e.g. droplet or micelle average size or sizedistribution) is obtained. Optionally, pre-mixing of the two or moreimmiscible liquids may be carried out or conducted through a magneticfield before transferring the resulting pre-mix to the liquid containingportion of the above-mentioned system.

The method of the invention may be carried out continuously orintermittently, the latter meaning with storage of the emulsion in theliquid containing portion of the emulsification system of the presentinvention after and before conducting or circulating the said emulsionthrough the one or more magnetic field(s). Intermittent circulationthrough the magnetic field may, for certain emulsions of two or moreliquids, allow improving the storage stability of the said emulsions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A represents a first embodiment of an emulsification system forperforming a method according to the invention.

FIG. 1B represents another embodiment of an emulsification system forperforming a method according to the invention.

FIG. 1C represents yet another embodiment of an emulsification systemfor performing a method according to the invention.

FIG. 1D represents yet another embodiment of an emulsification systemfor performing a method according to the invention.

FIG. 2 represents the distribution of relative masses of fat globules insemi-skimmed milk before and after 5 minutes or 10 minutes of a magnetictreatment according to the invention.

FIG. 3 represents the distribution of relative masses of lipid miscellesin whole milk before and after respectively 5 minutes, 10 minutes or 30minutes of a magnetic treatment according to the present invention.

FIG. 4 represents another embodiment of an emulsification system.

FIG. 5 represents the distribution of relative masses of micelles in a20% soybean oil emulsion after 20 minutes of a magnetic treatmentaccording to the invention.

FIG. 6 represents the distribution of relative masses of micelles in a60% soybean oil emulsion after 20 minutes of a magnetic treatmentaccording to the invention.

FIG. 7 represents the distribution of relative masses of micelles in afatty acid aqueous emulsion after 30 minutes or 60 minutes of a magnetictreatment according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be described with reference to certainembodiments and drawings but the present invention is not limitedthereto but only by the attached claims. The embodiments are given byway of example only.

The present invention relates to the unexpected finding that circulatingan unstable mixture of immiscible liquids through a magnetic field undersuitable conditions, such as magnetic field strength, temperature,number of re-circulation times and the like, results in a stableemulsion. Furthermore, various operational parameters of this methodwere identified as relevant to the efficiency of preparation of a stableemulsion and to the stability of the said emulsion. The influence ofsome of these parameters is detailed herein-after and illustrated in thefollowing examples.

A first embodiment of this invention relates to a method for preparingemulsions of two or more immiscible liquids by flowing, conducting orcirculating one or more times a pre-mix of said liquids, optionallyhaving solid particles suspended therein, through one or more magneticfields. The present invention also provides the use of equipment forperforming the method, i.e. an emulsification system comprising two ormore immiscible liquids, means for generating one or more magneticfields, and means for flowing or circulating said fluid one or moretimes through the said one or more magnetic fields. A means formeasuring the average size or size distribution of the emulsion dropletsor micelles may also be provided as a further component of theemulsification system of the invention.

The number of immiscible liquids is not a critical parameter of thepresent invention. For some emulsions, the presence of both at least ahydrophilic liquid, for instance an aqueous or nearly-aqueous phase, andat least a lipophilic (or hydrophobic) liquid is preferred. The chemicalnature, molecular size or other physical characteristic of thelipophilic (or hydrophobic) liquid is not critical. Such lipophilicliquids include, without limitation, edible oils (e.g. palm kernel oil,lauric oil, hydrogenated vegetable oils like soybean oil), fats andrelated products; fatty acids and esters thereof (including estersformed from a saturated or unsaturated linear or branched aliphaticalcohol having from 1 to 18 carbon atoms, in particular methyl or ethylesters, or from a saturated or unsaturated linear or branched aliphaticpolyol having from 2 to 6 carbon atoms, in particular glycerol,trimethylolpropane, sorbitan, sorbitol, pentaerythritol, neopentylglycol and mixtures thereof, or from a polyethyleneglycol orpolypropyleneglycol or methoxy polyethyleneglycol having a molecularweight up to 1,500), preferably natural or synthetic, saturated,mono-unsaturated or polyunsaturated acids having from 8 to 24 carbonatoms and optionally one or more functional groups such as hydroxy orepoxy such as caprylic, capric, lauric, myristic, palmitic, stearic,behenic, oleic, linoleic, linolenic, ricinoleic, arachidic, palmitoleic,stearidonic, arachidonic and isopalmitic acids; lipids of all kinds,including mono- and poly-acylglycerols, phosphoglycerides,sphingolipids, amino-amidines and the like, and mixtures thereof in allproportions, which are commonly used for making liposomes in the form ofmultilamellar or small unilamellar vesicles. As shown in examples below,the present invention is also applicable to the emulsification ofsaturated hydrocarbons having long carbon chain length such as, but notlimited to, dodecane.

It should be understood that the effect of the method of the inventionon the average size of droplets or micelles of the emulsion is moreimportant when the strength of the magnetic field is higher and/or thenumber of re-circulations through the magnetic field is higher. Sincethe strength of each commercially available magnet is usually limited toabout 10,000 gauss, a means to increase the effective magnetic field isto flow the suspension through a number of magnets arranged in series(especially for limiting or prolonging the duration of treatment) and/orto re-circulate the suspension several times, i.e. preferably at least10 times, more preferably at least 40 times, through the same magneticfield. Preferably the strength of each said magnetic field used forcarrying out the method of the invention is at least about 2,000 gaussat the active region thereof.

Whatever the nature and the number of immiscible liquids, flowing thepre-mix of said liquids through the magnetic field(s) is preferablyeffected at a temperature below the Curie temperature of the magneticmaterial used for generating said magnetic field(s), e.g. below about400° C. for a magnetic device of the Al-Ni-Co type. Flowing the pre-mixof said liquids through said magnetic field(s) is also preferablyeffected at a temperature between the freezing or solidifyingtemperature and the boiling temperature of said pre-mix under thepressure prevailing while flowing said pre-mix of liquids through saidmagnetic field(s). For instance, under atmospheric pressure, flowingsaid pre-mix of immiscible liquids through said magnetic field(s) ispreferably effected at a temperature between about 10° C. and about 90°C., for practical and economical reasons more preferably between about18° C. and about 70° C. The respective proportions of the immiscibleliquids in the pre-mix to be magnetically treated is not a criticalparameter of this invention and may be adapted, using standard practicein the art, depending upon the consumer product or industrialapplication which is targeted for the relevant emulsion. For instance,the proportion of the lipophilic liquid(s) in the pre-mix may be withina range from about 3 to about 60% by weight, preferably from 5 to 40% byweight, more preferably from 10 to 35% by weight, depending upon theexact nature of the said lipophilic liquid(s) and the optionalemulsifiers.

For certain pre-mix of immiscible liquids, it may be advantageous tocarry out the method of this invention in the presence of one or moreviscosity regulators and/or one or more emulsifiers or surfactants ofany class well known in the art, e.g. anionic surfactants, non-ionicsurfactants or cationic surfactants. The selection of suitableemulsifiers and the desirable amount thereof, depending upon the exactnature and amount of the said lipophilic liquid(s), are within theknowledge of those of ordinary skill in the art.

Suitable emulsifiers or surface-active agents include water-solublenatural soaps and water-soluble synthetic surface-active agents.Suitable soaps include alkaline or alkaline-earth metal salts,unsubstituted or substituted ammonium salts of higher fatty acids(C₁₀-C₂₂), e.g. the sodium or potassium salts of oleic or stearic acid,or of natural fatty acid mixtures obtainable form coconut oil or tallowoil. Synthetic surface-active agents (surfactants) include anionic,cationic and non-ionic surfactants, e.g. sodium or calcium salts ofpolyacrylic acid; sulphonated benzimidazole derivatives preferablycontaining 8 to 22 carbon atoms; alkylarylsulphonates; and fattysulphonates or sulphates, usually in the form of alkaline oralkaline-earth metal salts, unsubstituted ammonium salts or ammoniumsalts substituted with an alkyl or acyl radical having from 8 to 22carbon atoms, e.g. the sodium or calcium salt of lignosulphonic acid ordodecylsulphonic acid or a mixture of fatty alcohol sulphates obtainedfrom natural fatty acids, alkaline or alkaline-earth metal salts ofsulphuric or sulphonic acid esters (such as sodium lauryl sulphate) andsulphonic acids of fatty alcohol/ethylene oxide adducts. Examples ofalkylarylsulphonates are the sodium, calcium or alcanolamine salts ofdodecylbenzene sulphonic acid or dibutyl-naphtalenesulphonic acid or anaphtalene-sulphonic acid/formaldehyde condensation product. Alsosuitable are the corresponding phosphates, e.g. salts of phosphoric acidester and an adduct of p-nonylphenol with ethylene and/or propyleneoxide) and the like.

Suitable emulsifiers further include partial esters of fatty acids (e.g.lauric, palmitic, stearic or oleic) or hexitol anhydrides (e.g.,hexitans and hexides) derived from sorbitol, such as commerciallyavailable polysorbates. Other emulsifiers which may be employed include,but are not limited to, materials derived from adding polyoxyethylenechains to non-esterified hydroxyl groups of the above partial esters,such as Tween 60 commercially available from ICI Americas Inc.; and thepoly(oxyethylene) poly(oxypropylene) materials marketed by BASF underthe trade name Pluronic.

Preferably the method according to the invention involves re-circulatingtwo or more times the liquids through the magnetic field(s). The numberof re-circulation times may be quite high, e.g. up to 10,000 timesthrough one magnetic field, preferably up to 3,000 times through onemagnetic field, and may be easily adapted to the specific average sizetargeted for the droplets or micelles of an emulsion designed for acertain industrial or consumer product application. It is important thatthe liquids are flowed or circulated through the magnetic field(s) at aspeed which allows the magnetic treatment to effectively perform dropletor micelle formation to a significant extent within a specified periodof time. Preferably, the linear flow rate of said liquids through eachsaid magnetic field is between 0.25 and 25 m/s, more preferably between0.6 and 5 m/s. In view of the length of the magnetic field, it may becalculated that the residence time of said liquids through each saidmagnetic field is preferably between 60 microseconds and 10 seconds,depending upon the number or re-circulation times.

The present invention also provides an industrial process which, inaddition to including the above described emulsification method as aprocess step, may further comprise one or more post-processing steps.Said post-processing step may be a heating step or, especially forimproving the stability of the resulting emulsion, a cooling steppreferably to a temperature below room temperature, more preferably to atemperature within a range from about 2° C. to about 8° C. It is usuallyadvantageous to perform said cooling step until the moment when theemulsion is to be effectively used in the relevant final application.

In another embodiment, said post-processing step may be a drying step,which can be performed by any known drying technique, for at leastpartly removing the hydrophilic liquid from the emulsion. For instance,when the lipophilic phase liquid(s) consist of lipids suitable formaking liposomes, said post-processing step may be a freeze-drying stepsuitable for handling and storing the liposomes formed in the solidstate. In yet another variant of the is invention, the post-processingstep may be a step of diluting the emulsion through the addition of ahydrophilic liquid, preferably the same as originally used, into saidemulsion. In yet another variant of the invention, the post-processingstep may be a sonication step.

For quality control purpose, the industrial process of the invention mayfurther comprise one or more steps of controlling the size of dropletsor micelles produced during the emulsification method. In view of theorder of magnitude of the particle sizes involved, said size controllingstep is preferably performed by dynamic light scattering analysis. Whensaid industrial process comprises a post-processing step performedfollowing the emulsification step, it may further comprise one or moresteps of controlling the size of droplets or micelles produced during orafter said post-processing step, in which case said size controllingstep after said post-processing step may be performed by dynamic lightscattering analysis. The size controlling step may be performed in sucha way as to measure the average size and/or the size distribution of thedroplets or micelles produced during the various steps of saidindustrial process.

According to experience accumulated in the practice of the invention, itis estimated that the following parameters may affect the storagestability of the obtained emulsion:

-   -   emulsion stability may depend upon the linear flow rate of the        liquid mixture through the magnetic field(s). There seems to be        a threshold flow rate below which there is little or no        improvement in the stability of the pre-mixture. The gain in        emulsion stability increases with the said linear flow rate. A        transition from laminar flow to turbulent flow, and the        occurrence of undesired cavitation, may in most cases set the        maximum admissible linear flow rate. An optimum flow rate may        also exist and can be determined by the skilled for each        equipment without undue experimentation;    -   emulsion stability is usually improved when the number of        re-circulation times through the magnetic field(s) is raised.        Such improvement is mostly significant in the first set of        re-circulation times, however prolonged circulation has no        adverse effect. Below the threshold flow rate mentioned        hereinabove, raising the number of re-circulation times does not        help to improve the stability of the emulsion;    -   time elapsed between two re-circulation times through the        magnetic field while the mixture is in the liquid containing        portion or tubing may also affect the stability of the emulsion        produced. In a preferred embodiment, the pre-emulsion is treated        a number of times with short time intervals so as to reach        sufficient stability for storage;    -   shape of the liquid containing portion (reservoir) may also be        important, especially in order to ensure that the entire volume        of the emulsion is treated and to avoid zones where the pre-mix        may stagnate. Such stagnant zones comprising an emulsion pre-mix        with larger micelles can be responsible for coagulation and        phase separation of the emulsion.

The present invention also provides products having adequate or improvedstorage stability, such as detergents, cleaning products, lubricants,cosmetic, veterinary and pharmaceutical compositions (e.g. creams andointments) and food products, including an emulsion prepared accordingto the method described herein-above.

The present invention shows a number of advantages over the methods ofthe prior art. It achieves a substantial simplification in terms ofequipment and maintenance costs associated with the equipment requiredfor emulsification. It allows for easy access to and efficient controlof the desired emulsion characteristics (including, but not limited to,micelle size) and emulsion storage stability, whatever the nature of thelipophilic phase and its proportion in the emulsion. Thirdly, it iswidely applicable to all kinds of emulsions, including oil-in-water andwater-in-oil emulsions, as well as to the manufacturing of all kinds ofliposomes.

The following examples are provided for illustrating the principles andmethods of the invention but should not be construed as limiting thescope of the invention in any way.

EXAMPLE 1 Preparation of an Oil-in-Water Emulsion

0.930 kg of a fatty acid commercially available from Oleon (Belgium)under the trade name Radiacid 0166 and 0.061 kg of a surfactantcommercially available from Oleon (Belgium) under the trade nameRadiasurf 7403 were added to 2 kg of de-ionised water. The resultingpre-mix was vigorously stirred with an IKA RE16 mixer at 300 rpm, thenthe suspension was slowly heated to a temperature in the range of 60 to65° C. with an IKA RCT heater, said temperature being controlled bymeans of an IKA ETS-D4 apparatus. After 1 hour, temperature had reached60.7° C. Then, 11.7 g of a 50 weight % NaOH solution was added dropwisewhile continuing stirring of the mixture, resulting in a temperatureincrease up to 62.2° C. As a result, a white suspension was obtained.

The hot suspension was then magnetically treated in an emulsificationsystem schematically shown in FIG. 1A and which may be described asfollows. The system comprises a tubing (1); two external magneticdevices (2) arranged in series, commercially available from CEPI-CO(Antwerp, Belgium) under the trade name CEPI-SAN R1/2D and providing astrength of about 10,000 gauss, the said magnetic devices being mountedso as to create two consecutive orthogonal magnetic fields inside thefluid passing through; a pump (4) commercially available from ThermoElectron GmbH, Karlsruhe, Germany under the trade name Haake D8 anddisposed inside a reservoir (5) being a so-called Haake circulation bathfor receiving the suspension. The tubing (1) was attached to the pump(4) in such a way that the magnetic device (2) was in a downstreamdirection. The hot suspension was poured into the reservoir (5), whilemechanical stirring was immediately started by means of the IKA RE16mixer (not shown in FIG. 1A) operated at 200 rpm. The suspension waspumped through pump (4) at a speed of about 3 l/minute through themagnetic devices (2), and such treatment was continued for 360 minutes,while allowing the suspension to cool spontaneously.

Temperature of the mixture was measured during treatment and, at certainperiods of time, a sample of the treated suspension was taken and storedat room temperature (about 20° C.). Samples were kept in small glassvials (7 ml) for visual inspection. An overview of the sampling data(sample temperature and reference number) is given in table 1. TABLE 1time (min) temperature (° C.) sample  0 58.8 s0  15 51.6 s1  60 39.9 s2180 30.6 s3 360 28.8 s4

Sample s0 was separating quickly into a white yellow top layer and awhite water layer. Each of emulsion samples s1-4 appeared by eye to bestable after 6 hours. After overnight storage at room temperature, mostof the emulsion samples s1-4 showed some phase separation, although lesssignificant when a longer magnetic treatment was continued (i.e. samples4).

This experiment demonstrates that conducting a pre-mix of an aqueousphase and a lipophilic phase through a magnetic field under suitableconditions significantly improves the storage stability of the saidoil-in-water pre-mix.

EXAMPLE 2 Preparation of an Oil-in-Water Emulsion

In a first step, 1.163 kg of the same fatty acid and 0.076 kg of thesame surfactant as used in example 1 were added to 2.5 kg of de-ionisedwater. The resulting pre-mix was vigorously stirred with an IKA RE16mixer at 300 rpm. The suspension was then slowly heated to a temperatureof 63° C. with an IKA RCT heater. Temperature was controlled with an IKAETS-D4 apparatus. After temperature has reached 60.5° C., 14.62 g of a50% by weight NaOH solution was added dropwise to the suspension, whilecontinuing stirring of the mixture. The suspension was then allowed tocool to 40° C.

In a second step, 1.5 l of the suspension (still at a temperature of 40°C.) was poured into the liquid containing portion (5), having a 2 lvolume, of the emulsification system shown in FIG. 1B. Said liquidcontaining portion (5) consists of a cylindrical flask with a conicbottom to which a tubing (1 a) (commercially available under the tradename Masterflex Tygon lab I/P 70 from Cole-Parmer Instrument Company).By means of the pump (4) (commercially available from Cole-ParmerInstrument Company under the trade name Masterflex I/P) the suspensionwas pumped through tubing (1 b) to the top of the flask (5). Acommercial magnetic device (2) commercially available from CEPI-CO(Antwerp, Belgium) under the trade name CEPI-SAN R1/4D was attached tothe end of the tubing (1 b) at the inlet of the liquid containingportion (5). The pump (4) was continuously operated at a speed of 4.7l/minute for 60 minutes.

At certain periods of time (expressed in minutes), a sample of themagnetically treated suspension was taken in small glass vials (7 ml)for visual inspection and stored either at room temperature (in therange of 20 to 25° C.) or in the refrigerator (7° C.). Sample s0, with atime indication 0′, was taken at the outlet of the magnetic device (2)after one single pass of the suspension through the said device, whilesamples s1-s3 were taken in the flask (5). An overview of the samplingdata (sample reference numbers) is given in table 2. TABLE 2 time (min)sample room temp sample refrigerator   0′ s0 s′0 15 s1 s′1 30 s2 s′2 60s3 s′3

3.5 hours after sampling, s0 and s′0 showed phase segregation.Inspection of the samples s1, s′1, s2, s′2, s3 and s′3 showed that theywere still stable 21 hours after sampling but, after 92 hours storage,revealed some phase separation. This indicates that, under the presentexperimental conditions, a single pass of the suspension through themagnetic field provides very limited storage stability of the resultingemulsion.

EXAMPLE 3 Magnetic Treatment of a Fatty Acid Aqueous Pre-Mix

A fatty acid aqueous suspension was made exactly as in the first step ofexample 2. After further spontaneous cooling down and storing for 5 daysat room temperature (about 20° C.), the batch of the pre-mixedsuspension was stirred once more (by means of IKA RE16 operated at 300rpm) but not heated. Part of the batch was used for a blank experimentas explained below.

250 ml of the pre-mixed suspension (still at room temperature) waspoured into the liquid containing portion (5), having a 2 litre volume,of the emulsification system shown in FIG. 1C. Said liquid containingportion (5) consists of a cylindrical flask with a conic bottom. Acommercial magnetic device (2) (same as used in example 2) is mounted ina loop at the outlet of the liquid containing portion (5), except duringthe blank experiment. The loop consists of a tubing (1 a, 1 b) (sametype as used in example 2) which connects the magnetic device (2) to theinlet on top of the flask (5) via a pump (4) (same as used in example2). The said pump was continuously operated at a speed of 4.7 l/minute.

At certain periods of time (expressed in minutes), a sample of themagnetically treated suspension was taken at the end of the tubing (1 b)positioned at the inlet of the flask (5), the pump (4) being turned offduring sampling. Samples were kept in small glass vials (7 ml) forvisual inspection and stored either at room temperature (in the range of20 to 25° C.) or in the refrigerator (7° C.). An overview of thesampling data (sampling time, number of re-circulation times, and samplereference number) is given in table 3. The number of passages(re-circulation times) as given in table 3 was estimated based on thevolume of the pre-mixed suspension introduced into the flask and theflow speed. TABLE 3 sample time (min) number of passages room tempsample 7° C. experiment  0′  1 s0 s′0 with 1 12 s1 s′1 magnetic 2 24 s2s′2 device 15  180  s3 s′3 blank 2 24 b2 b′2 experiment 15  180  b3 b′3

All samples prepared with the magnetic device were emulsions, thestability of which depended on the treatment time. After 18 hoursstorage, sample s0 and s′0 showed some phase separation. Samples s1,s′1, s2 and s′2 were still stable after 22 hours, but their inspectionafter 42 hours revealed some phase separation. Sample s3 showed phaseseparation only 51 hours after treatment. 14 days after treatment,sample s′3 was still stable.

The storage stability of the samples of the blank experiment was clearlylower than that of the magnetically treated ones: samples b2, b′2, b3and b′3 showed phase separation within 20 hours after treatment. Thisdemonstrates that conducting an emulsion through a magnetic field underthe above experimental conditions significantly contributes to theformation of a stable emulsion.

EXAMPLE 4 Magnetic Treatment of a Fatty Acid Aqueous Pre-Mix

A fatty acid aqueous suspension was made exactly as in the first step ofexample 2. After further spontaneous cooling down and storing for 11days at room temperature (about 20° C.), the batch of the pre-mixedsuspension was stirred once more (by means of IKA RE16 operated at 300rpm) but not heated. Part of the batch was used for a blank experimentas explained below.

250 ml of the pre-mixed suspension (still at room temperature) wastreated in the emulsification system shown in FIG. 1C, the pump beingcontinuously operated at a speed of 6.3 l/minute, except that themagnetic device was not mounted in the loop during the blank experiment.After 1 hour of treatment, sampling of the emulsion was effected both atthe outlet of the tubing and in the flask (5). Samples were kept insmall glass vials (7 ml) for visual inspection and stored either at roomtemperature (at 25° C.) or in the refrigerator (7° C.). An overview ofthe sampling data (sampling location, sample reference number) is givenin table 4. TABLE 4 sampling sample room temp sample refrigeratorexperiment with reservoir s1 s′1 magnetic device tubing s2 s′2 blankexperiment reservoir b1 b′1 tubing b2 b′2Samples b′1 and b′2 were still stable after 96 hours storage. Phaseseparation occurred in samples b1 and b2 after 29.5 and 70 hoursrespectively. Samples s1 and s2 showed phase separation after 101 and165 hours of storage respectively. Samples s′1 and s′2 were still stableafter 197 hours of storage.

Improved storage stability was observed as compared to the previousexperiments of examples 2 and 3. This can be attributed to the higherpumping speed (with respect to example 3) or to the fact that theemulsion was pumped into the flask (5) through the magnetic device (withrespect to example 2).

EXAMPLE 5 Fatty Acid Emulsion Stability

A fatty acid aqueous suspension was made exactly as in the first step ofexample 2.

In a second step, 1.5 l of the suspension (still at a temperature of 40°C.) was poured into the liquid containing portion (5), having a 2 lvolume, of the emulsification system shown in FIG. 1C, the pump (4)being continuously operated at a speed of 4.7 l/minute. After 1 hourtreatment, the emulsion was pumped through the magnetic device into a 1litre glass Erlenmeyer where the sample was collected and stored at roomtemperature for further stability determination by visual inspection.The sample was found to be stable for more than 19 days, i.e.significantly more than the samples of example 3 being manufacturedunder the same conditions but stored in small glass vials. Thisindicates that factors such as surface to volume ratio, shape andchemical nature of the storage recipient can be critical for emulsionstability, especially when stability over long storage periods isdesired. Thus, evaluation of emulsion stability of emulsion samplesstored in small flasks such as in examples 1 to 3 rather represents akind of accelerated stability test.

EXAMPLE 6 Magnetic Treatment of Semi-Skimmed Milk

A semi-skimmed milk, manufactured by Stassano (Belgium) and containing1.6 g lipids/100 ml and 3.3 g proteins/100 ml was used in thisexperiment. The emulsification system used is shown in FIG. 1D andcomprises a cylindrical flask (5) with a conic bottom which is used as aliquid containing portion. A magnetic device (2) of the Al-Ni-Co type(same as used in example 2) and providing a strength of about 10,000gauss, is attached to the bottom of the flask (5) by means of a tubing(Masterflex Tygon lab I/P 70 from Cole-Parmer Instrument Company) insuch a way that the magnetic device is in a downstream direction. Thetubing (1 a, 1 b) connects the magnetic device (2) via the pump (4)(Masterflex I/P) with the inlet on top of the flask (5). The wholesystem is positioned in a box (6) filled with a mixture of water andice. The magnetic device (2), part of the tubing (1 a) and part of theflask (5) are immersed in the said mixture. This setup allows coolingmilk at a temperature below 20° C.

After 500 ml milk has been poured into flask (5), pump (4) is turned onand continuously operated at a flow rate of 4.7 l/minute, i.e. a linearvelocity of 1.1 m/s. Before treatment, and after 5 minutes and 10minutes of magnetic treatment respectively, samples were taken in theflask (5) for further analysis.

The size of fat micelles present in milk were analysed with diffusivelight scattering, using a high performance particle sizer with aHe-Ne-Laser (2,5 mW) from ALV Company. Measurements were performed withwater as standard reference for viscosity, and without making acorrection for viscosity, therefore micelles sizes should be interpretedas relative rather than absolute values, as shown in FIG. 2.

Three important effects of magnetic treatment are shown in FIG. 2:

-   -   a very significant reduction of the relative mass of micelles        sized between 5,000 and 45,000 nm. After 10 minutes of treatment        these large micelles have completely disappeared.    -   the peak of micelle size around 600 nm becomes sharper (i.e. a        narrower micelle size distribution around 600 nm) when treatment        time increases.    -   in the area of smallest micelles or particles average size, a        shift of the 20 nm peak (before treatment) clearly occurs        towards a 13 nm peak (after 5 minutes treatment) and a 9 nm peak        of significant importance (after 10 minutes treatment), i.e. a        more than 50% reduction in the average size of smallest        micelles.

EXAMPLE 7 Magnetic Treatment of Whole Milk

A whole milk, manufactured by Stassano (Belgium) and containing 3.6 glipids/100 ml and 3.3 g proteins/100 ml was used in this experiment. 400ml of this whole milk was treated in the same emulsification system asin example 6. Before treatment and after 5 minutes, 10 minutes and 30minutes of magnetic treatment respectively, samples were taken in theflask and analysed by the same technique as in example 6.

The effects of magnetic treatment are shown in FIG. 3:

-   -   the relative mass of lipid micelles with sizes between 4,000 and        53,000 nm is significantly reduced. After 10 minutes of        treatment these large micelles have almost entirely disappeared;    -   an increased presence of micelles having a particle size around        600 nm was observed, presumably due to the disruption of larger        micelles with sizes above 4,000 nm; and    -   a shift of the smallest micelles towards even smaller sizes may        be observed.

EXAMPLE 8 Magnetic Treatment of a Dodecane Water-in-Oil Emulsion

20 g of dodecane (commercially available from Acros Organics, 99%purity) and 1 g of a surfactant commercially available from Oleon(Belgium) under the trade name Radiamuls 2152 (previously heated toabout 40° C.) were mixed in a glass bottle, resulting in a transparentmixture. 80 g of bi-distilled water was then added and the bottle wasthoroughly shaken, resulting in a milky white emulsion. This emulsionwas magnetically treated in the emulsification system shown in FIG. 4and comprising, within a loop, a tubing (1) (Masterflex Tygon lab I/P 70from Cole Parmer Instrument Company), a magnetic device (2) of theAl-Ni-Co type and providing a strength of about 10,000 gauss (same asused in example 2) and a 3-way horizontal ball valve (3) (commerciallyavailable from Georg Fischer Rohrleitungssysteme AG under the trade name343 DN10/15). The tubing (1) was attached to a pump (4) (Masterflex I/P)in such a way the magnetic device (2) was in a downstream direction. Thetotal volume of this system is 0,100 l. Part of the system is placed ina box (6) cooled with a mixture of water and ice. As a result theemulsion temperature is kept below room temperature during treatment.The emulsion was magnetically treated during 20 minutes while applying apumping speed of 4.7 l/minute (corresponding to a linear flow rate of1.1 m/s).

The magnetically treated emulsion was sampled at room temperature, thesample (s2) was inspected visually and compared to the correspondingsample (s1) taken before treatment, both samples being collected andkept in a 120 ml glass bottle. Sample s1 shows phase separation within 2hours, including a transparent watery top layer. Sample s2 was stillstable after 94 hours, its phase separation occurring only after 118hours.

EXAMPLE 9 Magnetic Treatment of a 20% Soybean Oil Emulsion

20 g of a soybean oil (commercially available from Lesieur) and 5 g ofthe same surfactant Radiasurf 7403 already used in example 1 were mixedin a glass bottle, resulting in a turbid yellow mixture. 80 g ofbi-distilled water was added and the bottle was thoroughly shaken,resulting in a white-yellow emulsion.

This emulsion was magnetically treated in the emulsification systemshown in FIG. 4 at the same pumping speed of 4.7 l/minute. Themagnetically treated emulsion was sampled at room temperature, thesample (s2) was inspected visually and compared to the correspondingsample (s1) taken before treatment. Improvement in storage stability wassignificant, since s1 showed phase separation only 5 minutes afterpreparation, whereas s2 was still stable after 3 hours storage at roomtemperature and showed de-mixing only after 13.5 hours storage. Samples2 was also analysed by diffusive light scattering under the sameconditions as in example 6. FIG. 5 shows the micelle size distributionof sample s2 in the range from 30 nm to 100,000 nm. Two major micellesizes are present in this emulsion: the most important fraction size isaround an average of 1,100 nm, whilst a second minor fraction with anaverage size of about 65 nm is also present. The peak at 100,000 nm isdue to mathematical processing and is therefore not representative ofsample composition.

EXAMPLE 10 Magnetic Treatment of a 60% Soybean Oil Emulsion

60 g of a soybean oil (commercially available from Lesieur) and 5 g ofthe same surfactant Radiasurf 7403 already used in example 1 were mixedin a glass bottle, resulting in a yellow mixture. 40 g of bi-distilledwater was added and the bottle was thoroughly shaken, resulting in aturbid yellowish emulsion.

This emulsion was magnetically treated in the emulsification systemshown in FIG. 4 at the same pumping speed of 4.7 l/minute. Themagnetically treated emulsion was sampled at room temperature, thesample (s4) was inspected visually and compared to the correspondingsample (s3) taken before treatment. Improvement in storage stability wassignificant, since s3 showed phase separation only 60 minutes afterpreparation, whereas s4 was still stable after 18 hours storage at roomtemperature and showed de-mixing only after 109 hours storage. Sample s4was also analysed by diffusive light scattering under the sameconditions as in example 6. FIG. 6 shows the micelle size distributionof sample s4 in the range from 10 nm to 100,000 nm. Two major micellesizes are present in this emulsion: the most important fraction size isaround an average of 950 nm, whilst a second minor fraction with anaverage size of about 15 nm is also present. The peak at 100,000 nm isdue to mathematical processing and is therefore not representative ofsample composition.

EXAMPLE 11 Preparation of an Oil-in-Water Emulsion

A fatty acid aqueous suspension was made exactly as in the first step ofexample 2.

In a second step, the said suspension (still at a temperature of 40° C.)was treated in the emulsification system shown in FIG. 4, the pump (4)being continuously operated at a speed of 1.7 l/minute (corresponding toa linear flow rate of 0.4 m/s).

At certain periods of time (expressed in minutes), a sample of themagnetically treated suspension was taken and stored either at roomtemperature (in the range of about 25 to 30° C.) or in the refrigerator(7° C.) for visual inspection or dynamic light scattering (DLS)analysis, using the same technique as in example 6. An overview of thesampling data (sampling reference numbers) is given in table 5. Samples′2, with a time indication 0′, indicates a sample taken shortly afterpouring the emulsion into the tubing system (in doing so, the pump wasturned on a few times, meaning the liquid had yet passed through themagnetic device a few times). TABLE 5 time (min) sample room temp samplerefrigerator DLS   0′ s1 s′1  0 s′2 15 s′3 30 s′4 s″4 60 s5 s′5 s″5

Samples s1 and s′1 separated quickly into a white yellow top layer and awhite water layer. Sample s′2 separated similarly 4 hours later. Samples′3 was de-mixed after 14 hours. Samples s′4, s5 and s′5 remainedhomogeneous for at least 72 hours but were de-mixed after 138 hours.

FIG. 7 shows the distribution of relative masses of the micelles (in therange from 10 nm to 2,000 nm) of samples s″4 and s″5 obtained after 30minutes and 60 minutes treatment respectively. This clearly shows anarrowing of the distribution around an average size of about 150 nmupon prolonged magnetic treatment for 1 hour.

1-30. (canceled)
 31. An emulsification method comprising flowing,conducting or circulating a pre-mix of two or more immiscible liquidsthrough one or more magnetic fields under conditions to emulsify saidpre-mix, wherein said pre-mix of two or more immiscible liquids is milkor comprises at least a hydrophilic liquid and at least a lipophilicliquid, wherein said lipophilic liquid is selected from the groupconsisting of edible oils, fats, fatty acids and esters thereof formedfrom a saturated or unsaturated linear or branched aliphatic alcoholhaving from 1 to 18 carbon atoms or from a saturated or unsaturatedlinear or branched aliphatic polyol having from 2 to 6 carbon atoms orfrom a polyethyleneglycol or polypropyleneglycol or methoxypolyethyleneglycol having a molecular weight up to 1,500; natural orsynthetic, saturated, mono-unsaturated or polyunsaturated acids havingfrom 8 to 24 carbon atoms and optionally one or more functional groupssuch as hydroxy or epoxy; lipids including mono- and polyacylglycerols,phosphoglycerides, sphingolipids, amino-amidines, and mixtures thereof,and wherein the linear flow rate of said liquids through each saidmagnetic field is between 0.25 and 25 m/s.
 32. An emulsification methodaccording to claim 31, wherein said hydrophilic liquid is an aqueous ornearly-aqueous phase.
 33. An emulsification method according to claim31, wherein said pre-mix further comprises one or more viscosityregulators and/or one or more emulsifiers or emulsion stabilizers orsurfactants.
 34. An emulsification method according to claim 31, whereinsaid pre-mix further comprises solid particles suspended therein. 35.mulsification method according to claim 31, wherein the strength of eachsaid magnetic field is at least 2,000 gauss.
 36. An emulsificationmethod according to claim 31, wherein said hydrophilic liquid is anaqueous or nearly-aqueous phase and wherein the proportion of saidlipophilic liquid in said pre-mix is within a range from 3 to 60% byweight.
 37. An emulsification method according to claim 31, wherein saidpremix of two or more immiscible liquids is re-circulated from 10 to10,000 times through each said magnetic field.
 38. An emulsificationmethod according to claim 31, wherein the linear flow rate of saidliquids through each said magnetic field is between 0.6 and 5 m/s. 39.An emulsification method according to claim 31, wherein the residencetime of said fluid through each said magnetic field is between 60microseconds and 10 seconds.
 40. An emulsification method according toclaim 31, wherein flowing said liquids through said magnetic field(s) iseffected at a temperature between 10° C. and 90° C.
 41. An industrialprocess including an emulsification method according to claim 31 as aprocess step.
 42. An industrial process according to claim 41, whereinsaid process further comprises one or more post-processing stepsperformed following the emulsification step.
 43. An industrial processaccording to claim 41, wherein said process further comprises a dryingstep for at least partially removing the hydrophilic liquid present inthe emulsification step.
 44. An industrial process according to claim41, wherein said process further comprises one or more steps ofcontrolling the size of droplets or micelles produced during theemulsification step.
 45. An industrial process according to claim 41,wherein said process further comprises one or more steps of controllingthe size of droplets or micelles produced during the emulsification stepand wherein said size controlling step is performed by dynamic lightscattering analysis.
 46. An industrial process according to claim 41,wherein said process further comprises a sonication step.
 47. Anindustrial process according to claim 41, wherein said process furthercomprises a cooling step or a heating step.
 48. An industrial processaccording to claim 41, wherein said process further comprises afreeze-drying step.
 49. An emulsification method according to claim 31,wherein said pre-mix of two or more immiscible liquids is milk, wherebythe average size of the smallest micelles or particles contained in milkis decreased by at least 50%.